POS0886 EFFICACY AND SAFETY OF RITUXIMAB IN AUTOIMMUNE DISEASE–ASSOCIATED INTERSTITIAL LUNG DISEASE: A PROSPECTIVE COHORT STUDY.
Authors: N. Mena-Vázquez, C. M. Romero-Barco, M. Rojas-Giménez, R. Redondo, I. Ureña, I. Añón Oñate, P. Morales-Garrido, L. Pérez Albaladejo, M. Velloso Feijoo, M. D. C. Ordoñez Cañizares, S. Manrique Arija
Journal: Annals of the Rheumatic Diseases (2022)

Background Interstitial lung disease (ILD) is a common condition in patients with connective tissue disease (CTD). It is associated with increased morbidity and mortality. Rituximab (RTX) has been approved for treatment of RA and some recent retrospective studies suggest that it could be an alternative treatment for patients with CTD-ILD, even in cases that prove refractory to conventional immunosuppressants. Objectives To analyze the efficacy and safety of RTX in connective tissue disease associated with interstitial lung disease (CTD-ILD). Methods We performed a multicenter, prospective, observational study of patients with CTD-ILD receiving RTX between 2015 and 2020. Patients who had worsening of respiratory symptoms or decline in the pulmonary function tests (PFT) compared to the time of ILD diagnosis were treated with rituximab. The patients were assessed using high-resolution computed tomography and PFT baseline, at 12 months, and at the end of follow-up. The main outcome measure at the end of follow-up was forced vital capacity (FVC)&gt;10% or diffusing capacity of the lungs for carbon monoxide (DLCO)&gt;15% and radiological progression or death. We recorded clinical characteristics, time to initiation of RTX, concomitant treatment, infections, and hospitalization. A Cox regression analysis was performed to identify factors associated with worsening of ILD. Results We included 37 patients with CTD-ILD treated with RTX for a median (IQR) of 38.2 (17.7-69.0) months (Table 1). At the end of the follow-up, disease had improved or stabilized in 23 patients (62.1%) and worsened in 7 (18.9%); 7 patients (18.9%) died. Mean PFT values decreased significantly at the start of RTX compared to the date of ILD diagnosis in FVC (72.2[21.3]vs 73.5 [16.9] mg/l;p=0.040) and DLCO-SB (55.9 [15.7] vs 58.3 [16.1] mg/l; p=0.041). No significant decline was observed in median FVC (72.2 vs 70.8; p=0.530) or DLCO (55.9 vs 52.2; p=0.100). The multivariate analysis showed the independent predictors for worsening of CTD-ILD to be baseline DLCO (OR [95% CI], 0.904 [0.8-0.9]; p=0.015), time to initiation of RTX (1.01 [1.001-1.02]; p=0.029), and mycophenolate (0.202 [0.04-0.8]; p=0.034). The infection incidence rate was 0.21 patient-years. Table 1. Baseline demographic and clinical characteristics of 37 patients with CTD-ILD receiving rituximab. Variable Total n=37 RAn=19 SSn=14 IMn=4 p Value Female sex, n (%) 27 (73.0) 13 (68.4) 11 (78.6) 3 (75.0) 0.806 Age in years, mean (SD) 62.8 (9.9) 67.7 (9.7) 57.9 (7.9) 56.6 (5.5) 0.001 Smoking 0.147 Never smoked, n (%) 20 (54.1) 9 (47.4) 7 (50.0) 4 (100.0) Smoked at some time, n (%) 17 (45.9) 10 (52.6) 7 (50.0) 0 (0.0) Duration of CTD, months, median (IQR) 107.8 (49.5-188.8) 151.0 (8.,0-240.5) 89.6 (51.3-184.4) 35.1 (25.1-49.0) 0.017 Duration of ILD, months, median (IQR) 65.4 (31.1-110.3) 82.2 (37.4-120.1) 64.5 (35.5-107.1) 25.9 (25.0-36.0) 0.136 Time to initiation of RTX, median (IRQ) 12.0 (6.5-48.2) 25.1 (7.0-57.6) 11.4 (3.9-43.6) 7.4 (7.0-10.4) 0.455 Duration of treatment with RTX, median (IQR) 38.2 (23.4-69.9) 45.3 (22.2-79.9) 52.5 (24.7-63.3) 22.8 (17.7-36.2) 0.291 Combined with csDMARDs, n (%) 15 (40.5) 9 (47.4) 5 (35.7) 1 (25.0) 0.637 Methotrexate, n (%) 5 (13.5) 2 (10.5) 3 (21.4) 0 (0.0) 0.468 Leflunomide, n (%) 2 (5.4) 2 (10.5) 0 (0.0) 0 (0.0) 0.367 Sulfasalazine, n (%) 1 (2.7) 1 (5.3) 0 (0.0) 0 (0.0) 0.615 Hydroxychloroquine, n (%) 7 (18.9) 4 (21.1) 2 (14.3) 1 (25.0) 0.840 Combination with immunosuppressants, n (%) 20 (54.1) 7 (36.8) 9 (64.3) 4 (100.0) 0.044 Mycophenolate, n (%) 19 (51.4) 6 (31.6) 9 (64.3) 4 (100.0) 0.021 Azathioprine, n (%) 1 (2.7) 1 (5.3) 0 (0.0) 0 (0.0) 0.615 Corticosteroids, n (%) 25 (67.6) 14 (73.7) 7 (50.0) 4 (100.0) 0.121 Doses of corticosteroids, median (IQR) 5.0 (0.0-10.0) 5.0 (0.0-10.0) 2.5 (0.0-7.5) 10.0 (8.1-10.5) 0.519 Conclusion Lung function improved or stabilized in more than half of patients with CTD-ILD treated with RTX. No significant increase in infection rates was observed. Early treatment and combination with mycophenolate could reduce the risk of progression of ILD. Disclosure of Interests None declared